CPSI Biotech is a medical device company that specializes in thermal ablation systems for treating a variety of cancers. The SCN systems developed by CPSI are now in prototype form and have been animal tested at a variety of venues including Johns Hopkins School of Medicine. CPSI also specializes in novel probes and catheters designed for the cryoablation of cancers for use with the SCN system. This Phase 1 SBIR application proposes to develop a new device and treatment regime for treating pancreatic cancer (PaCa). CPSI has named this new approach ERASE (Endoscopic-based combinatoRial Ablative and Sensitization therapeutic procedurE). The project includes the development of a (1) next gen dual thermal ablation (DTA) catheter with an integrated intertumoral drug delivery channel (QuadProbe) and requisite re-engineering of the SCN system as well as (2) identifying thermal sensitizers that will make DTA more effective. Under Phase 1 studies the investigational team will identify and test the effectiveness of the targeted chemical molecular sensitizers in conjunction with the SCN and QuadProbe catheter to develop ERASE to more effectively treat resectable and nonresectable PaCa. Further, through the incorporation of select site directed drug therapy the combinatorial ERASE protocol will help address the challenges with the management of metastatic disease targeting undetected satellite cancer populations. The intent of this project is to develop and characterize a next generation, flexible, closed loop, needle catheter-based endoscopic device (QuadProbe) for the treatment of PaCa employing a minimally invasive outpatient procedure. The prototype device and preliminary data collected to date strongly support the potential of this approach. The major goals of this Phase 1 proposal are to (1) develop the QuadProbe DTA catheter, (2) identify a series of drugs that when used with DTA increase the destruction of PaCa cells, (3) develop the combinatorial drug/ablation ERASE protocol, (4) optimize ERASE in an ex vivo tissue model, and (5) conduct a pilot in vivo study for validation and technology/procedural development. Phase 2 studies will be dedicated to optimizing the four-way function of the QuadProbe (freezing, heat, thermal sentizer ejection, biopsy/tissue aspirate collection) as well as working with our Johns Hopkins colleagues analyzing and modulating the immune response triggered in patients who have undergone the ERASE protocol so that patient outcome can be improved. The successful completion of this project will lead to new technology and therapy for the management of PaCa as well as provide data in support of establishing the thermal dose parameters necessary for optimal clinical application of the proposed, as well as other, ablation devices for the treatment of PaCa. This project will leverage and combine the expertise of researchers from CPSI, Binghamton University, and Johns Hopkins School of Medicine to develop a new surgical/sensitizer approach to more effectively treat PaCa. Once completed, this project will provide for an effective, minimally invasive treatment option for individuals suffering from PaCa contributing to efforts for improving patient survival and quality of life.